CARRIER AND PRENATAL DIAGNOSIS OF MENKES DISEASE

Gu YH1,2 , Kodama H1, Murata Y1, Ushijima H2

1 Dept. of Pediatrics, Teikyo University School of Medicine, Tokyo, Japan

2 Dept. of Developmental Medical Sciences, School of International Health, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan

 

Objective: Menkes disease (MND) is an X-linked recessive neurodegenerative disorder caused by defects in ATP7A gene. To MND early diagnosis are very important because initiating treatment over 2 months old is not effective in preventing the neurological degeneration. We report here the carrier and prenatal diagnosis performed in 6 families.

Methods: When the ATP7A mutation in a family is known, genomic DNA was analyzed by PCR and direct sequencing for the presence or absence of the mutant allele in 5 mothers, 1 maternal aunt and 3 female fetuses. For the family mutation has not been found, the copper concentration in cultured amniotic cells of a male fetus was measured using an atomic absorption spectrometry.

Results: Three of the 5 mothers are carriers; 2 are normal. A patient¡¯s maternal aunt is a carrier. DNA analysis revealed that the fetuses in 3 families are females and are not carriers. The 3 fetuses were born as normal individuals. One male fetus was suspected as an affected child because his copper concentration in the cultured fibroblasts confirmed that he is a patient with MND. He received an early treatment and presented normal.

Conclusion: Molecular diagnosis of carrier females and at-risk pregnancies is fast and reliable because random inactivation of one of the X-chromosomes may cause normal clinical and biochemical features in carrier. Measuring copper concentration in cultured amniotic fluid cells is also a useful parameter for prenatal diagnosis.

 
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